2 Key 49ers Starters Will Miss a Couple of Weeks Due to Injury

The 49ers will have to take on the Texans and Giants without these two key starters after they suffered hamstring injuries versus the Falcons.

Oct 19, 2025; Santa Clara, California, USA; San Francisco 49ers head coach Kyle Shanahan walks along the sideline during the second quarter against the Atlanta Falcons at Levi's Stadium. Mandatory Credit: Darren Yamashita-Imagn Images | Darren Yamashita-Imagn Images

It just wouldn't be a normal Monday for the San Francisco 49ers without a new injury popping up.

Kyle Shanahan revealed via conference call on Monday that pass rusher Bryce Huff suffered a hamstring injury in the win against the Atlanta Falcons.

Starting center Jake Brendel, who exited the game, is also dealing with a hamstring injury. Both Huff and Brendel are expected to miss a couple of weeks.

That means 49ers fans should not expect them to be active against the Houston Texans and the New York Giants. Just a typical 49ers Monday that deflates the win from the previous day.

What the 49ers will do to work around the absences

Sep 28, 2025; Santa Clara, California, USA; San Francisco 49ers defensive end Bryce Huff (47) gestures during the second quarter against the Jacksonville Jaguars at Levi's Stadium. Mandatory Credit: Darren Yamashita-Imagn Images | Darren Yamashita-Imagn Images

As has been the theme of 2025, the 49ers will go with the next man up with Huff and Brendel out. Although, Huff being ouit is going to be the most difficult to overcome of the two.

The 49ers' pass rush was already ineffective without Nick Bosa until they played the Falcons. Huff seemed like he was finding his footing again now that he attracts a lot of attention.

Against Atlanta, Huff tallied a season-high six pressures and strip-sack. He was an absolute monster for the Falcons offensive line and Michael Penix.

Now, the 49ers will be without him for at least two weeks. Losing Brendel isn't as much as a bummer. Matt Hennessy filled in for him and seemed okay.

The only question with Hennessy is if he is cerebrally sound. Playing center for Kyle Shanahan requires a strong intellect.

He proved to be capable against the Falcons, but as we've seen with rookie Connor Colby, things change when you have to fill in for a starter versus when you are the starter.

Sep 28, 2025; Santa Clara, California, USA; San Francisco 49ers center Jake Brendel (64) before the game against the Jacksonville Jaguars at Levi's Stadium. Mandatory Credit: Darren Yamashita-Imagn Images | Darren Yamashita-Imagn Images

Nevertheless, these injuries continue to be the common trend of 2025 for the 49ers. It was believed that their injury luck would spike for them this year after how bad it was for them in 2024.

But this season has arguably been way worse with injuries. Somehow, the 49ers have done a tremendous job staying afloat, which is why they are 5-2.

I'd expect Robert Saleh to keep his foot on the pedal with the blitzing with Huff out. The 49ers should be fine without Huff against the Texans. Their offensive line is one of the worst in the NFL.

On the flip side, the Texans have a strong defensive front. Mac Jones might be in a little trouble without his starting center. But with how well the 49ers have operated with key starters out, I wouldn't fret too much over this.

Follow Jose on X (Twitter) @JS3sanchez_to interact with him on the 49ers.

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